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Rhinovirus uses a phosphatidylinositol 4-phosphate/cholesterol counter-current for the formation of replication compartments at the ER-Golgi interface.

Abstract
Similar to other positive-strand RNA viruses, rhinovirus, the causative agent of the common cold, replicates on a web of cytoplasmic membranes, orchestrated by host proteins and lipids. The host pathways that facilitate the formation and function of the replication membranes and complexes are poorly understood. We show that rhinovirus replication depends on host factors driving phosphatidylinositol 4-phosphate (PI4P)-cholesterol counter-currents at viral replication membranes. Depending on the virus type, replication required phosphatidylinositol 4-kinase class 3beta (PI4K3b), cholesteryl-esterase hormone-sensitive lipase (HSL) or oxysterol-binding protein (OSBP)-like 1, 2, 5, 9, or 11 associated with lipid droplets, endosomes, or Golgi. Replication invariably required OSBP1, which shuttles cholesterol and PI4P between ER and Golgi at membrane contact sites. Infection also required ER-associated PI4P phosphatase Sac1 and phosphatidylinositol (PI) transfer protein beta (PITPb) shunting PI between ER-Golgi. These data support a PI4P-cholesterol counter-flux model for rhinovirus replication.
AuthorsPascal S Roulin, Mark Lötzerich, Federico Torta, Lukas B Tanner, Frank J M van Kuppeveld, Markus R Wenk, Urs F Greber
JournalCell host & microbe (Cell Host Microbe) Vol. 16 Issue 5 Pg. 677-90 (Nov 12 2014) ISSN: 1934-6069 [Electronic] United States
PMID25525797 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2014 Elsevier Inc. All rights reserved.
Chemical References
  • Phosphatidylinositol Phosphates
  • Receptors, Steroid
  • VAPB protein, human
  • Vesicular Transport Proteins
  • oxysterol binding protein
  • phosphatidylinositol 4-phosphate
  • Cholesterol
Topics
  • Cell Membrane (metabolism)
  • Cell Nucleus (metabolism)
  • Cells, Cultured
  • Cholesterol (metabolism)
  • Golgi Apparatus (metabolism)
  • Host-Pathogen Interactions
  • Humans
  • Phosphatidylinositol Phosphates (metabolism)
  • Receptors, Steroid (metabolism)
  • Rhinovirus (enzymology, physiology)
  • Vesicular Transport Proteins (metabolism)
  • Virus Replication

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